Systemic inflammation response index (SIRI) on the 3rd postoperative day are associated with severe pneumonia in cerebral hemorrhage patients: A single-center retrospective study

Inflammatory response was involved in the progression of cerebral hemorrhage. We sought to explore the associations of easily obtained inflammatory indicators including blood cell counts and the ratios of different blood cells counts with pneumonia and severe pneumonia in cerebral hemorrhage patients. We carried 1 retrospective study including 200 patients with cerebral hemorrhage and surgeries. The associations of neutrophils, lymphocytes, monocytes, platelets, systemic immune inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) with pneumonia and severe pneumonia in cerebral hemorrhage patients were estimated by univariate analysis and multivariate logistic regression model. Among the 200 patients included, there were a total of 163 (81.5%) had pneumonia after surgeries. Among 163 cerebral hemorrhage patients with pneumonia, 60 (36.8%) cases were evaluated as severe pneumonia. The level of SIRI on the 1st postoperative day in patients with severe pneumonia was higher than non-severe pneumonia (10.89 ± 12.10 × 109/L vs 7.14 ± 9.76 × 109/L, P = .003). The level of SIRI on the 3rd postoperative day in patients with severe pneumonia was more significantly higher (7.98 ± 7.46 × 109/L vs 4.10 ± 3.74 × 109/L, P < .001). The results of multivariate analysis showed that SIRI level on the 3rd postoperative day (>6.5 × 109/L) was associated with severe pneumonia in cerebral hemorrhage patients (OR: 4.409, 95% CI: 1.799–10.806, P = .001). SIRI was possibly a superior predictor for severe pneumonia in cerebral hemorrhage patients compared with other inflammatory indicators. On the one hand, we intend to validate the cutoff value of SIRI for predicting severe pneumonia in larger samples and multicenter studies. On the other hand, we also intend to use this index to guide the choice of antibacterial drugs in order to better benefit patients.


Introduction
Cerebral hemorrhage was a common type of stroke.Cerebral hemorrhage accounted for approximately 50% of stroke. [1,2] survey of 480,687 participants from 155 urban and rural centers in 31 provinces of China showed that the incidence of spontaneous intracranial hemorrhage was 23.8%. [3]The mortality of cerebral hemorrhage was possibly 40% after 30 days of onset. [4]Only about 20% of patients could recover and take care of themselves after 6 months, [5] bringing a heavy burden to society and families.Pneumonia was one common complication of cerebral hemorrhage.The incidence of pneumonia in elderly patients with cerebral hemorrhage was 25.6%. [6]In the intensive care unit, 42% of patients with intracerebral hemorrhage were diagnosed with ventilator associated pneumonia. [7]There were about 66% of patients with cerebral hemorrhage developing hospital acquired pneumonia between 2nd to 5th days during YZ and XW contributed equally to this work.

The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.Supplemental Digital Content is available for this article.
hospitalization. [8]Concomitant pneumonia possibly affected the outcomes of patients with cerebral hemorrhage, the mortality rate could reach 18%. [7]n recent years, some studies have explored the associations between inflammatory factors and concomitant pneumonia in cerebral hemorrhage patients.In the study by Dzhulaĭ GS et al, the results showed that interleukin-1 alpha level both in serum and cerebrospinal fluid increased in the presence of nosocomial pneumonia since the first day of stroke.Interleukin-1 alpha level could be an early risk factor of poor outcome in patients with cerebral hemorrhage. [8]Among 329 patients with cerebral hemorrhage included in the analysis by Alsumrain M. et al, there were 183 (55.6%) cases developing pneumonia.The results of univariate and multivariate logistic regression showed that levels of NLR and PLR at admission were independent predictors of pneumonia. [5]There were also studies showing that SIRI at admission was associated with pneumonia in cerebral hemorrhage patients. [9]The analysis of receiver operating characteristic curve (ROC) in 1 study showed that NLR at admission was the best predictor of stroke associated pneumonia compared with other inflammatory indicators. [10]However, there were few studies focusing on the associations between postoperative inflammatory indicators with concomitant pneumonia or severe pneumonia in cerebral hemorrhage patients with surgeries, which was the objective of our study.

Patients
One retrospective study was conducted in the department of neurosurgery, the First Affiliated Hospital of Yangtze University from January 2019 to April 2023.Our study complied with the requirements of the Ethics Committee.In addition, the study was reported in line with the STROBE guidelines and was conducted in accordance with the Declaration of Helsinki.Patients were included if they met the following criteria: aged ≥ 18 years; having cerebral hemorrhage confirmed by computed tomography (CT); admitted 48 hours after onset and undergoing surgeries within 48 hours after admission.Patients were excluded if they met the following criteria: dead within 48 hours of admission; diagnosed with pneumonia by CT before admission; diagnosed with subarachnoid hemorrhage by CT; diagnosed with hemorrhage after ischemic stroke; with hematologic diseases; with severe renal dysfunction, liver dysfunction, and immunosuppression.The flowchart was showed in Figure 1.

Data collection
The following baseline characteristics were collected from all included patients: demographic characteristics, combination of lung diseases (emphysema or pulmonary bulla, bronchiectasis, rib fracture, etc), score of Glasgow coma scale (GCS) at admission (a lower score indicating a poor level of consciousness), combination of ventricular hemorrhage at admission and surgical duration.
Laboratory data including neutrophil count, lymphocyte count, monocyte count, and platelet count at 3 time points (preoperative, the 1st postoperative, and the 3rd postoperative days) were collected and analyzed, which was completed in the laboratory of hospital.Counts of blood cells on these days were obtained by flow cytometry (Sysmex XN-9000 Blood Analyzer, Japan).We calculated NLR, PLR, SII and SIRI based on the above blood test results.NLR = neutrophil count/lymphocyte The flow chart of the study.Among all included patients, a total of 163 (81.5%) had pneumonia after surgeries.Among 163 patients with pneumonia, 60 (36.8%) cases were evaluated as severe pneumonia.
We referred to the diagnostic and treatment guidelines for hospital-acquired pneumonia in adult in China for diagnosis.The diagnosis of pneumonia and severe pneumonia in patients required 2 experienced physicians to jointly evaluate.The patient was diagnosed with pneumonia or severe pneumonia according to respiratory symptoms, signs, chest CT or X-ray results, and laboratory examinations, but also met the following conditions.The results of chest CT or X-ray showed new or progressive infiltrative shadows, consolidation shadows, or ground glass shadows, plus 2 or more of the following criteria: fever (body temperature ≥ 38˚C); purulent airway secretions; white blood cell count ≥ 10 × 10 9 /L or < 4 × 10 9 /L.If the patient needed tracheal intubation for mechanical ventilation, or had septic shock, he would be diagnosed as severe pneumonia.Other secondary criteria for severe pneumonia included: respiratory rate ≥30 per minute, oxygenation index ≤250 mm Hg, multiple lobar infiltration, disorders of consciousness, disorientation, blood urea nitrogen ≥7.14 mmol/L, systolic blood pressure <90 mm Hg. [11][12][13] 2.3.Statistical analysis SPSS 23.0 (IBM SPSS Inc., Chicago, USA) was used for data analysis.The qualitative variables were compared by Pearson chi-square test, Continuity correction or Fisher exact test.If the quantitative variables met the normal distribution and variances were homogeneous, independent-sample t-test was used for analysis.If the quantitative variables met the normal distribution but variances were not homogeneous, corrected t-test was used.If the normal distribution could not be satisfied, Mann-Whitney U test was used for analysis.The multivariate logistic regression model was constructed for factors with pneumonia or severe pneumonia in cerebral hemorrhage patients.Covariates that had a P value <.05 in the univariate analysis were added to the multivariate logistic analysis.The receiver operating characteristic curve (ROC) was used for the cutoff value analysis.All P values were 2-sided and the statistical significance was set at P < .05.

Baseline characteristics
Among the 200 patients included, 158 were males and 42 were females.The median age was 61 years.There were 56 patients with lung diseases, including 13 cases with rib fracture, 8 cases with bronchiectasis and 35 cases with emphysema.There were 65 cases with GCS score <11, and 48 cases with intraventricular hemorrhage (Table 1).The median surgical duration was 115 minutes.Among all patients, the preoperative NLR level was 7.29 ± 10.15, PLR level was 165.63 ± 141.33, SIRI level was 4.05 ± 6.27 × 10 9 /L, and SII level was 1254.27 ± 1895.80 × 10 9 /L (Table 2).

Factors associated with severe pneumonia
Among 163 patients with pneumonia, 60 (36.8%) cases were evaluated as severe pneumonia, and 103 (63.2%) cases were evaluated as non-severe pneumonia.Among patients with severe pneumonia, there were 48 males and 12 females.The median age was 64 years old.There were 19 cases with lung diseases.The median surgical duration in patients with severe pneumonia was 160 minutes, significantly longer than patients with non-severe pneumonia (100 minutes), P < .001.Among patients with severe pneumonia, 70% (42/60) had a GCS score < 11, significantly more than patients with non-severe pneumonia, P < .001(Table 1).The preoperative platelet count was 167 ± 69 × 10 9 /L in these patients with severe pneumonia, lower than patients with non-severe pneumonia (193 ± 73 × 10 9 /L, P = .022).The PLR levels in patients with severe pneumonia, non-severe pneumonia were 136.85 ± 145.47 and 181.12 ± 162.71 respectively (P = .035).There were no significant differences in levels of neutrophils, lymphocytes, monocytes, SII, SIRI and NLR in these patients (P > .05)(Table 3).

Discussions
The association between inflammatory factor and pneumonia in cerebral hemorrhage patients has been a hot topic in recent years.In our study, we explored the associations of inflammatory factors from blood cell counts on preoperative, 1st postoperative and 3rd postoperative days with pneumonia and severe pneumonia in cerebral hemorrhage patients.The disruption of the balance between neutrophils and lymphocytes could exacerbate inflammatory responses.NLR is the ratio of neutrophils to lymphocytes, which is a new inflammatory indicator and with simplicity and convenience.Among patients with acute cerebral infarction, the NLR levels varied among patients with different infarction areas. [14]Among patients with acute cerebral hemorrhage, the level of NLR was significantly higher in dead patients than in survivors. [15]The results of 1 study in mice model of cerebral hemorrhage by injecting autologous blood into striatum showed that 36.4% cerebral hemorrhage mice had spontaneous pneumonia and/ or bloodstream infections, while sham surgery mice had no infectious complications. [16]In 1 study involving 146 patients with acute pancreatitis, a significant increase of NLR level at admission was associated with severe acute pancreatitis. [17]The levels of NLR possibly varied at different times of cerebral hemorrhage.There were few studies on the associations between postoperative pneumonia and NLR levels at different times.In the study by Wang RH, [10] the result showed that NLR at admission was the best predictive factor for stroke associated   pneumonia.The univariate analysis results in our study found that NLR levels on the 1st and 3rd postoperative days were associated with pneumonia in cerebral hemorrhage patients.However, the multivariate analysis did not find the associations between NLR at different times and pneumonia.Different NLR levels were possibly consistent with the severity of disease.In the study of endocarditis patients, NLR > 5.035 was associated with severe sepsis. [18]Our study also explored the associations between NLR at different times with severe pneumonia in cerebral hemorrhage patients.Unfortunately, only the univariate analysis showed a association between NLR level on the 1st postoperative day with severe pneumonia.PLR was the ratio of platelet to lymphocyte.In malignant tumor patients, PLR level was possibly associated with the prognosis and treatment response to anti-tumor drugs.In endometrial cancer patients, PLR ≥ 134.95 was associated with invasion of myometrium ≥50%. [19]In advanced non-small cell lung cancer patients, higher PLR level was an independent risk factor associated with the first-line chemotherapy efficacy and clinical prognosis. [20]In addition to tumors, the results of other studies also confirmed the association between PLR level and infection.In patients with urinary tract infection, the PLR level was 176.645 ± 110.051, significantly higher than patients without urinary tract infection (121.945± 53.735). [21]In patients with COVID-19, PLR level was the only factor associated with mortality. [22]Our study explored the association between PLR level and postoperative pneumonia in cerebral hemorrhage patients.The univariate analysis results showed a significant association between PLR level on the 3rd postoperative day and pneumonia in cerebral hemorrhage patients.But the multivariate analysis result did not find this significant association.In the study by Ravindra R. et al, the PLR level in patients with severe infection was significantly higher than patients with mild infection. [23]ur study explored the associations between PLR levels at different times and severe pneumonia in cerebral hemorrhage patients.The results of univariate analysis showed a significant difference in PLR levels between severe and non-severe pneumonia patients.However, the multivariate analysis did not show any association.
There were also some studies showing a association between SII level and prognosis.Higher SII level (>390 × 10 9 /L) was a powerful indicator for tumor differentiation and 1-year survival rate in newly diagnosed solid tumor patients. [24]In pancreatic cancer and small cell lung cancer patients, significant increase of SII level was associated with a shorter overall survival. [25,26]mong 18,609 stroke patients included in 19 retrospective studies, higher SII level was significantly associated with poor outcome. [27]Among 362 ischemic stroke patients, SII was an independent risk factor for stroke severity. [28]There were few studies on the associations between SII levels at different times and pneumonia in cerebral hemorrhage patients.Our study explored these associations, only the univariate analysis results showed that preoperative and postoperative levels of SII were associated with pneumonia and severe pneumonia.
Systemic inflammatory response index (SIRI) was based on counts of neutrophils, monocytes and lymphocytes.It was also showed to be associated with the prognosis of patients with malignant tumors.In breast cancer patients, lower SIRI was associated with higher overall survival when compared with higher SIRI. [29]In gallbladder cancer patients, SIRI level was also an independent prognostic indicator. [30]In pancreatic cancer patients, cases with SIRI ≥ 2.3 × 10 9 /L were more likely to benefit from mFOLFIRINOX treatment. [31]Stroke is a disease with high mortality.The results of 1 study including 2450 stroke patients showed that higher SIRI level was associated with higher all-cause mortality.The increase in SIRI was associated with higher mortality and stroke severity, as well as higher sepsis risk. [32]In study by Yu T. et al, [9] the results showed an association between higher SIRI level at admission and pneumonia in cerebral hemorrhage patients.
In our study, the result of univariate analysis confirmed this association.We also confirmed an association between SIRI level on the 3rd postoperative day and pneumonia in these patients by univariate analysis.But the multivariate analysis did not confirm these results.Our study firstly explored the association between SIRI level and severe pneumonia in cerebral hemorrhage patients.Both univariate and multivariate analyses confirmed an association between SIRI level on the 3rd postoperative day and severe pneumonia in cerebral hemorrhage patients.
Our study also had several limitations.First, the preoperative levels of inflammatory factors in most patients were on the 1st preoperative day, in a very few patients were on the 2nd preoperative day, which possibly resulted a bias.Second, the study only investigated the associations of blood cell counts and related indicators with pneumonia in cerebral hemorrhage patients, but did not investigate other inflammatory indicators including C-reactive protein, interleukin-6 and other inflammatory factors.Third, the sample size was not big enough, and we will expand the sample size for the next step.

Conclusion
SIRI was possibly a superior predictor for severe pneumonia in cerebral hemorrhage patients compared with other inflammatory indicators.On the one hand, we intend to validate the cutoff value of SIRI for predicting severe pneumonia in larger samples and multicenter studies.On the other hand, we also intend to use this index to guide the choice of antibacterial drugs in order to better benefit patients.

Figure 1 .
Figure1.The flow chart of the study.Among all included patients, a total of 163 (81.5%) had pneumonia after surgeries.Among 163 patients with pneumonia, 60 (36.8%) cases were evaluated as severe pneumonia.

Figure 2 .
Figure2.The result of ROC analysis of SIRI level on the 3rd postoperative day in patients with severe pneumonia.The cutoff value of the 3rd postoperative SIRI level for predicting severe pneumonia was 6.5 × 10 9 /L.The area under the curve was 0.692 (95% CI, 0.6-0.783,P < .001).The sensitivity was 64.4%, and the specificity was 76.3%.ROC = receiver operating characteristic curve, SIRI = Systemic inflammation response index.

Table 1
Baseline clinical characteristics in all patients.

Table 2
Levels of inflammatory indicators in patients with pneumonia and without pneumonia.

Table 3
Levels of inflammatory indicators in patients with severe pneumonia and non-severe pneumonia.